{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T21:57:54Z","timestamp":1790546274303,"version":"4.1.0"},"reference-count":43,"publisher":"The Company of Biologists","issue":"11","license":[{"start":{"date-parts":[[2020,9,4]],"date-time":"2020-09-04T00:00:00Z","timestamp":1599177600000},"content-version":"vor","delay-in-days":1403,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["SAF2011\/22555"],"award-info":[{"award-number":["SAF2011\/22555"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["SAF2014-51795-R"],"award-info":[{"award-number":["SAF2014-51795-R"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012818","name":"Comunidad de Madrid","doi-asserted-by":"crossref","award":["S2010\/BMD-2423"],"award-info":[{"award-number":["S2010\/BMD-2423"]}],"id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CIBER de Diabetes y Enfermedades Metab\u00f3licas Asociadas","award":["PIE14\/00061"],"award-info":[{"award-number":["PIE14\/00061"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Type 2 diabetes mellitus is a complex metabolic disease and its pathogenesis involves abnormalities in both peripheral insulin action and insulin secretion. Previous in vitro data showed that insulin receptor isoform A, but not B, favours basal glucose uptake through its specific association with endogenous GLUT1\/2 in murine hepatocytes and beta cells. With this background, we hypothesized that hepatic expression of insulin receptor isoform A in a mouse model of type 2 diabetes could potentially increase the glucose uptake of these cells, decreasing the hyperglycaemia and therefore ameliorating the diabetic phenotype. To assure this hypothesis, we have developed recombinant adeno-associated viral vectors expressing insulin receptor isoform A (IRA) or isoform B (IRB) under the control of a hepatocyte\u00ad-specific promoter. Our results demonstrate that in the long term, hepatic expression of IRA in diabetic mice is more efficient than IRB in ameliorating glucose intolerance. Consequently, it impairs the induction of compensatory mechanisms through beta cell hyperplasia and\/or hypertrophy that finally lead to beta cell failure, reverting the diabetic phenotype in about 8\u2005weeks. Our data suggest that long-term hepatic expression of IRA could be a promising therapeutic approach for the treatment of type 2 diabetes mellitus.<\/jats:p>","DOI":"10.1242\/dmm.025288","type":"journal-article","created":{"date-parts":[[2016,8,26]],"date-time":"2016-08-26T00:39:07Z","timestamp":1472171947000},"page":"1271-1281","source":"Crossref","is-referenced-by-count":18,"title":["Insulin receptor isoform A ameliorates long-term glucose intolerance in diabetic mice"],"prefix":"10.1242","volume":"9","author":[{"given":"Sabela","family":"Diaz-Castroverde","sequence":"first","affiliation":[{"name":"School of Pharmacy, Complutense University of Madrid 1 Department of Biochemistry and Molecular Biology II , , Madrid 28040 , Spain"},{"name":"CIBER of Diabetes and Related Diseases (CIBERDEM), Health Institute Carlos III (ISCIII) 2 , Madrid 28029 , Spain"},{"name":"Mechanisms of Insulin Resistance Consortium (MOIR) 3 , Madrid 28040 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almudena","family":"G\u00f3mez-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Complutense University of Madrid 1 Department of Biochemistry and Molecular Biology II , , Madrid 28040 , Spain"},{"name":"CIBER of Diabetes and Related Diseases (CIBERDEM), Health Institute Carlos III (ISCIII) 2 , Madrid 28029 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Complutense University of Madrid 1 Department of Biochemistry and Molecular Biology II , , Madrid 28040 , Spain"},{"name":"CIBER of Diabetes and Related Diseases (CIBERDEM), Health Institute Carlos III (ISCIII) 2 , Madrid 28029 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gema","family":"Garc\u00eda-G\u00f3mez","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Complutense University of Madrid 1 Department of Biochemistry and Molecular Biology II , , Madrid 28040 , Spain"},{"name":"CIBER of Diabetes and Related Diseases (CIBERDEM), Health Institute Carlos III (ISCIII) 2 , Madrid 28029 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Di Scala","sequence":"additional","affiliation":[{"name":"Center for Applied Medical Research, University of Navarra 4 Division of Hepatology and Gene Therapy , , Pamplona, Navarra 31008 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Gonz\u00e1lez-Aseguinolaza","sequence":"additional","affiliation":[{"name":"Center for Applied Medical Research, University of Navarra 4 Division of Hepatology and Gene Therapy , , Pamplona, Navarra 31008 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Fern\u00e1ndez-Mill\u00e1n","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Complutense University of Madrid 1 Department of Biochemistry and Molecular Biology II , , Madrid 28040 , Spain"},{"name":"CIBER of Diabetes and Related Diseases (CIBERDEM), Health Institute Carlos III (ISCIII) 2 , Madrid 28029 , Spain"},{"name":"Mechanisms of Insulin Resistance Consortium (MOIR) 3 , Madrid 28040 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1gueda","family":"Gonz\u00e1lez-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Liver Research Unit, Hospital Universitario Santa Cristina, Instituto de Investigaci\u00f3n Sanitaria Princesa 5 , Amadeo Vives 2, Madrid 28009 , Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) 6 , Health Institute Carlos III (ISCIII), Madrid 28029 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Garc\u00eda-Bravo","sequence":"additional","affiliation":[{"name":"CIEMAT\u2013CIBER of Rare Diseases (CIBERER)\u2013Institute of Health Investigation Jim\u00e9nez D\u00edaz Foundation (IIS-FJD) 7 Differentiation and Cytometry Unit, Hematopoietic Innovative Therapies Division , , Madrid 28040 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Chambon","sequence":"additional","affiliation":[{"name":"Institute of Genetic and Molecular and Cellular Biology (CNRS UMR7104; INSERM U596; ULP, Coll\u00e9ge de France) and Mouse Clinical Institute 8 , Illkirch, Strasbourg 67400 , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"\u00c1lvarez","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Complutense University of Madrid 1 Department of Biochemistry and Molecular Biology II , , Madrid 28040 , Spain"},{"name":"CIBER of Diabetes and Related Diseases (CIBERDEM), Health Institute Carlos III (ISCIII) 2 , Madrid 28029 , Spain"},{"name":"Mechanisms of Insulin Resistance Consortium (MOIR) 3 , Madrid 28040 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Perdomo","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Complutense University of Madrid 1 Department of Biochemistry and Molecular Biology II , , Madrid 28040 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Beneit","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Complutense University of Madrid 1 Department of Biochemistry and Molecular Biology II , , Madrid 28040 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8249-1645","authenticated-orcid":false,"given":"Oscar","family":"Escribano","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Complutense University of Madrid 1 Department of Biochemistry and Molecular Biology II , , Madrid 28040 , Spain"},{"name":"CIBER of Diabetes and Related Diseases (CIBERDEM), Health Institute Carlos III (ISCIII) 2 , Madrid 28029 , Spain"},{"name":"Mechanisms of Insulin Resistance Consortium (MOIR) 3 , Madrid 28040 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Benito","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Complutense University of Madrid 1 Department of Biochemistry and Molecular Biology II , , Madrid 28040 , Spain"},{"name":"CIBER of Diabetes and Related Diseases (CIBERDEM), Health Institute Carlos III (ISCIII) 2 , Madrid 28029 , Spain"},{"name":"Mechanisms of Insulin Resistance Consortium (MOIR) 3 , Madrid 28040 , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2024061302503096700_DMM025288C1","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1038\/gt.2008.64","article-title":"Potential of AAV vectors in the treatment of metabolic disease","volume":"15","author":"Alexander","year":"2008","journal-title":"Gene Ther."},{"key":"2024061302503096700_DMM025288C2","doi-asserted-by":"publisher","first-page":"3219","DOI":"10.1128\/MCB.01489-08","article-title":"Glucose effects on beta-cell growth and survival require activation of insulin receptors and insulin receptor substrate 2","volume":"29","author":"Assmann","year":"2009","journal-title":"Mol. Cell. Biol."},{"key":"2024061302503096700_DMM025288C3","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1042\/BJ20061709","article-title":"Characterization of insulin\/IGF hybrid receptors: contributions of the insulin receptor L2 and Fn1 domains and the alternatively spliced exon 11 sequence to ligand binding and receptor activation","volume":"403","author":"Benyoucef","year":"2007","journal-title":"Biochem. J."},{"key":"2024061302503096700_DMM025288C4","doi-asserted-by":"publisher","first-page":"e0119270","DOI":"10.1371\/journal.pone.0119270","article-title":"Aberrant liver insulin receptor isoform A expression normalises with remission of type 2 diabetes after gastric bypass surgery","volume":"5","author":"Besic","year":"2015","journal-title":"PLoS ONE"},{"key":"2024061302503096700_DMM025288C5","doi-asserted-by":"publisher","first-page":"49","DOI":"10.2337\/diab.38.1.49","article-title":"Compensatory growth of pancreatic beta-cells in adult rats after short-term glucose infusion","volume":"38","author":"Bonner-Weir","year":"1989","journal-title":"Diabetes"},{"key":"2024061302503096700_DMM025288C6","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.cmet.2007.12.009","article-title":"Selective versus total insulin resistance: a pathogenic paradox","volume":"7","author":"Brown","year":"2008","journal-title":"Cell Metab."},{"key":"2024061302503096700_DMM025288C7","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/S1097-2765(00)80155-0","article-title":"A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance","volume":"2","author":"Br\u00fcning","year":"1998","journal-title":"Mol. Cell"},{"key":"2024061302503096700_DMM025288C8","doi-asserted-by":"publisher","first-page":"2122","DOI":"10.1126\/science.289.5487.2122","article-title":"Role of brain insulin receptor in control of body weight and reproduction","volume":"289","author":"Br\u00fcning","year":"2000","journal-title":"Science"},{"key":"2024061302503096700_DMM025288C9","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.2337\/db12-1113","article-title":"Treatment of diabetes and long-term survival after insulin and glucokinase gene therapy","volume":"62","author":"Callejas","year":"2013","journal-title":"Diabetes"},{"key":"2024061302503096700_DMM025288C10","doi-asserted-by":"publisher","first-page":"3974","DOI":"10.1158\/0008-5472.CAN-12-3824","article-title":"Mitogenic insulin receptor-A is overexpressed in human hepatocellular carcinoma due to EGFR-mediated dysregulation of RNA splicing factors","volume":"73","author":"Chettouh","year":"2013","journal-title":"Cancer Res."},{"key":"2024061302503096700_DMM025288C11","doi-asserted-by":"publisher","first-page":"13972","DOI":"10.1074\/jbc.M115.638197","article-title":"Pathogenesis of selective insulin resistance in isolated hepatocytes","volume":"290","author":"Cook","year":"2015","journal-title":"J. Biol. Chem."},{"key":"2024061302503096700_DMM025288C12","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1016\/j.ceb.2007.09.015","article-title":"Formation and regeneration of the endocrine pancreas","volume":"19","author":"Dhawan","year":"2007","journal-title":"Curr. Opin. Cell Biol."},{"key":"2024061302503096700_DMM025288C13","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.celrep.2013.01.007","article-title":"Liver-derived systemic factors drive beta cell hyperplasia in insulin-resistant states","volume":"3","author":"El Ouaamari","year":"2013","journal-title":"Cell Rep."},{"key":"2024061302503096700_DMM025288C14","doi-asserted-by":"publisher","first-page":"820","DOI":"10.2337\/db08-0551","article-title":"Beta-Cell hyperplasia induced by hepatic insulin resistance: role of a liver-pancreas endocrine axis through insulin receptor A isoform","volume":"58","author":"Escribano","year":"2009","journal-title":"Diabetes"},{"key":"2024061302503096700_DMM025288C15","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.mce.2015.03.008","article-title":"Insulin receptor isoform A confers a higher proliferative capability to pancreatic beta cells enabling glucose availability and IGF-I signaling","volume":"409","author":"Escribano","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"2024061302503096700_DMM025288C16","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0021-9258(18)64849-5","article-title":"A simple method for the isolation and purification of total lipides from animal tissues","volume":"226","author":"Folch","year":"1957","journal-title":"J. Biol. Chem."},{"key":"2024061302503096700_DMM025288C17","doi-asserted-by":"publisher","first-page":"3278","DOI":"10.1128\/MCB.19.5.3278","article-title":"Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells","volume":"19","author":"Frasca","year":"1999","journal-title":"Mol. Cell. Biol."},{"key":"2024061302503096700_DMM025288C18","doi-asserted-by":"publisher","first-page":"e67748","DOI":"10.1371\/journal.pone.0067748","article-title":"IL12-mediated liver inflammation reduces the formation of AAV transcriptionally active forms but has no effect over preexisting AAV transgene expression","volume":"8","author":"Gil-Fari\u00f1a","year":"2013","journal-title":"PLoS ONE"},{"key":"2024061302503096700_DMM025288C19","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1210\/en.2008-1003","article-title":"Prolactin receptor is required for normal glucose homeostasis and modulation of beta-cell mass during pregnancy","volume":"150","author":"Huang","year":"2009","journal-title":"Endocrinology"},{"key":"2024061302503096700_DMM025288C20","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.2337\/diab.43.8.1066","article-title":"Banting Lecture. Insulin action, diabetogenes, and the cause of type II diabetes","volume":"43","author":"Kahn","year":"1994","journal-title":"Diabetes"},{"key":"2024061302503096700_DMM025288C21","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1038\/373384a0","article-title":"Diabetes. Causes of insulin resistance","volume":"373","author":"Kahn","year":"1995","journal-title":"Nature"},{"key":"2024061302503096700_DMM025288C22","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/S1525-0016(02)00060-6","article-title":"In vitro and in vivo comparative study of chimeric liver-specific promoters","volume":"7","author":"Kramer","year":"2003","journal-title":"Mol. Ther."},{"key":"2024061302503096700_DMM025288C23","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/S0092-8674(00)80546-2","article-title":"Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes","volume":"96","author":"Kulkarni","year":"1999","journal-title":"Cell"},{"key":"2024061302503096700_DMM025288C24","doi-asserted-by":"publisher","first-page":"2615","DOI":"10.1002\/cncr.26559","article-title":"Association between tamoxifen treatment and diabetes: a population-based study","volume":"118","author":"Lipscombe","year":"2012","journal-title":"Cancer"},{"key":"2024061302503096700_DMM025288C25","doi-asserted-by":"publisher","first-page":"93","DOI":"10.3389\/fendo.2011.00093","article-title":"The insulin receptor: a new target for cancer therapy","volume":"2","author":"Malaguarnera","year":"2011","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"2024061302503096700_DMM025288C26","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.2337\/db07-1369","article-title":"Beta-cell replication is the primary mechanism subserving the postnatal expansion of beta-cell mass in humans","volume":"57","author":"Meier","year":"2008","journal-title":"Diabetes"},{"key":"2024061302503096700_DMM025288C27","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1038\/nature11781","article-title":"How insulin engages its primary binding site on the insulin receptor","volume":"493","author":"Menting","year":"2013","journal-title":"Nature"},{"key":"2024061302503096700_DMM025288C28","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/S1097-2765(05)00015-8","article-title":"Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction","volume":"6","author":"Michael","year":"2000","journal-title":"Mol. Cell"},{"key":"2024061302503096700_DMM025288C29","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1677\/JME-09-0045","article-title":"Maternal undernutrition increases pancreatic IGF-2 and partially suppresses the physiological wave of beta-cell apoptosis during the neonatal period","volume":"44","author":"Miguel-Santos","year":"2010","journal-title":"J. Mol. Endocrinol."},{"key":"2024061302503096700_DMM025288C30","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/nrm2327","article-title":"Mechanisms of disease: molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes","volume":"9","author":"Muoio","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2024061302503096700_DMM025288C31","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1093\/ilar.47.3.199","article-title":"Molecular approaches to study control of glucose homeostasis","volume":"47","author":"Neubauer","year":"2006","journal-title":"ILAR J."},{"key":"2024061302503096700_DMM025288C32","doi-asserted-by":"publisher","first-page":"3709","DOI":"10.1210\/en.2005-1663","article-title":"Role of insulin receptor in the regulation of glucose uptake in neonatal hepatocytes","volume":"147","author":"Nevado","year":"2006","journal-title":"Endocrinology"},{"key":"2024061302503096700_DMM025288C33","doi-asserted-by":"publisher","first-page":"E234","DOI":"10.1210\/jc.2010-0932","article-title":"Significant human beta-cell turnover is limited to the first three decades of life as determined by in vivo thymidine analog incorporation and radiocarbon dating","volume":"95","author":"Perl","year":"2010","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"2024061302503096700_DMM025288C34","doi-asserted-by":"publisher","first-page":"2994","DOI":"10.1210\/en.139.6.2994","article-title":"Apoptosis in the pancreatic islet cells of the neonatal rat is associated with a reduced expression of insulin-like growth factor II that may act as a survival factor","volume":"6","author":"Petrik","year":"1998","journal-title":"Endocrinology"},{"key":"2024061302503096700_DMM025288C35","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.tem.2009.11.001","article-title":"Expansion of beta-cell mass in response to pregnancy","volume":"21","author":"Rieck","year":"2010","journal-title":"Trends Endocrinol. Metab."},{"key":"2024061302503096700_DMM025288C36","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/414799a","article-title":"Insulin signalling and the regulation of glucose and lipid metabolism","volume":"414","author":"Saltiel","year":"2001","journal-title":"Nature"},{"key":"2024061302503096700_DMM025288C37","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1210\/en.138.4.1736","article-title":"Apoptosis participates in the remodeling of the endocrine pancreas in the neonatal rat","volume":"138","author":"Scaglia","year":"1997","journal-title":"Endocrinology"},{"key":"2024061302503096700_DMM025288C38","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/gene.20039","article-title":"Efficient temporally controlled targeted somatic mutagenesis in hepatocytes of the mouse","volume":"39","author":"Schuler","year":"2004","journal-title":"Genesis"},{"key":"2024061302503096700_DMM025288C39","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1055\/s-2007-979040","article-title":"Adaptation of islets of Langerhans to pregnancy: beta-cell growth, enhanced insulin secretion and the role of lactogenic hormones","volume":"29","author":"Sorenson","year":"1997","journal-title":"Horm. Metab. Res."},{"key":"2024061302503096700_DMM025288C40","doi-asserted-by":"publisher","first-page":"2557","DOI":"10.2337\/diabetes.54.9.2557","article-title":"Very slow turnover of beta-cells in aged adult mice","volume":"54","author":"Teta","year":"2005","journal-title":"Diabetes"},{"key":"2024061302503096700_DMM025288C41","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1210\/mend.12.5.0106","article-title":"Insulin receptor substrate (IRS) proteins IRS-1 and IRS-2 differential signaling in the insulin\/insulin-like growth factor-I pathways in fetal brown adipocytes","volume":"12","author":"Valverde","year":"1998","journal-title":"Mol. Endocrinol."},{"key":"2024061302503096700_DMM025288C42","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1002\/bies.200800210","article-title":"Ligand-induced activation of the insulin receptor: a multi-step process involving structural changes in both the ligand and the receptor","volume":"31","author":"Ward","year":"2009","journal-title":"Bioessays"},{"key":"2024061302503096700_DMM025288C43","doi-asserted-by":"publisher","first-page":"47380","DOI":"10.1074\/jbc.M208371200","article-title":"Comparison of the functional insulin binding epitopes of the A and B isoforms of the insulin receptor","volume":"277","author":"Whittaker","year":"2002","journal-title":"J. Biol. Chem."}],"container-title":["Disease Models &amp; Mechanisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1242\/dmm.025288","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/9\/11\/1271\/3485534\/dmm025288.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dmm\/article-pdf\/doi\/10.1242\/dmm.025288\/2069440\/dmm_025288v1.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dmm\/article-pdf\/9\/11\/1271\/3485534\/dmm025288.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T02:50:52Z","timestamp":1718247052000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dmm\/article\/9\/11\/1271\/20111\/Insulin-receptor-isoform-A-ameliorates-long-term"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,1]]},"references-count":43,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2016,11,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dmm.025288","relation":{},"ISSN":["1754-8411","1754-8403"],"issn-type":[{"value":"1754-8411","type":"electronic"},{"value":"1754-8403","type":"print"}],"subject":[],"published":{"date-parts":[[2016,11,1]]}}}